The FGF family currently consists of seven members. The most widely studied molecules to date, acidic and basic FGF (aFGF and bFGF), are two structurally related polypeptides of molecular weight 15000-18000 kD. They were isolated originally from bovine brain, pituitary and retinal tissues but are also present in many other tissues. Basic FGF is a mitogenic factor for most cells of mesodermal and ectodermal origin via binding to specific cell surface receptors. Indeed, high and low affinity binding sites for bFGF have been identified in baby hamster kidney (BHK) cells and many other cell types including bovine lens epithelial cells (BEL cells). Basic FGF also binds to basement membranes in a dose dependent manner probably on the polysaccharide part of the heparan sulfate proteoglycans.
Recent studies have established the feasibility of conferring cytotoxic activities to bFGF by chemically conjugating potential toxins to the growth factor. As an example, saporin is a ribosome inactivating protein isolated from Saponaria officinalis which can be chemically conjugated to bFGF. The resulting bFGF-saporin conjugate (bFGF-SAP) is a specific cytotoxin for cells expressing the bFGF receptor (Lappi et al., Biochem. Biophys. Res. Commun. 160: 2, 917-923, 1989; Lappi et al, J. Cell. Physiol. 147, 17-26, 1991). Because the coupling between saporin and bFGF does not affect bFGF affinity for heparin or its high affinity receptor, the conjugate has all the characteristics of the mitogen. WO 90/125597 discloses conjugates comprising a cytotoxic agent and a polypeptide reactive with a FGF receptor, for example bFGF-SAP, for use in treating FGF-mediated pathophysiological conditions such as tumours, atherosclerosis, rheumatoid arthritis and proliferative retinopathy.
The present invention, however, is concerned with the treatment of another pathological condition. This condition is a side-effect of cataract surgery, in particular cataract surgery performed by a technique which leaves the posterior part of the lens capsule in place. The purpose of leaving in place the posterior part of the lens capsule is to maintain the vitreous fluid at its place in the eye and, most of the time, to anchor the lens implant.
In many instances, the lens cells which are left at the periphery migrate and divide. They then occupy the center of the lens capsule and impair vision. This can occur in about 30% of cases within several months in young patients or within a year in old patients. New surgery or laser treatment is needed to break the membrane that forms, which is costly and not harmless.
We have found that a bFGF-SAP conjugate is bound tightly to a lens capsule. The presence of the conjugate prevents the migration and proliferation of epithelial lens cells. Other eye tissue, such as the corneal endothelium which controls corneal transparency, is not damaged. These findings have general applicability.